19-Nordeoxycorticosterone (19-norDOC) has been found to show much higher hypertensive activity compared to deoxycorticosterone (DOC) [Funder et al., Endocrinology, 103, 1514 (1978)]. It is equipotent to aldosterone in stimulating Na.sup.+ transport across toad bladder epithelia [Perrone et al., Am. J. Physiol., 41, E406 (1981)] and has two to five times the potency of DOC in Na-retaining activity [Kagawa et al., Soc. Exp. Biol. Med., 94, 444 (1957)].
19-norDOC has been isolated from rats with adrenal regenerating hypertension (ARH) [Gomez-Sanchez et al., Endocrinology, 105, 708 (1979)] and from humans [Dale et al., Steroids, 37, 103 (1981)]. Elevated excretion of the compound has been reported for three hypertensive rat models: ARH, spontaneously hypertensive rats (SHR) and the salt-susceptible inbred Dahl rat [Griffing et al., Endocrinology, 121, 645 (1987); Dale et al., Endocrinology, 110, 1989 (1982); Gomez-Sanchez et al., J. Steroid Biochem., 25, 106 (1986)]. Increased levels of urinary 19-norDOC have been observed for several classes of human hypertensives [Griffing et al., J. Clin. Endocrinol. Metab., 56, 218 (1983)].
In the biosynthetic formation of 19-norsteroids, such as 19-norDOC, the initial step is the adrenal 19-hydroxylation of an appropriate steroid such as DOC. Thus, the inhibition of the biosynthetic formation of 19-norDOC by inhibition of 19-hydroxylation of DOC would thus serve to decrease the level of 19-norDOC present in the animal involved and reduce hypertensive effects attributable to the presence of this material.
It has further been shown that 10-(2-propynyl)estr-4-ene-3,17-dione (a known aromatase inhibitor and a 19-hydroxylase inhibitor) retards the development of hypertension and reduces the levels of urinary free 19-norDOC when administered to weanling SHR rats [Melby et al., Hypertension, 10, 484 (1987)].